New Breast Cancer vaccine
Researchers at the University of Pennsylvania, working under the leadership of Brian Czerniecki, have shown that a short course of vaccination with their own anti-HER2 dendritic cells of patients in about 20% leads to the complete destruction of an early form of breast cancer – ductal carcinoma in situ. After vaccination, more than 85% of patients developed a persistent immune response, which may reduce the risk of developing more severe forms of the disease in the future.
According to Dr. Chernietski, previous attempts to create a vaccine were directed against tissue antigens expressed by tumor cells, but not necessary for their survival. Therefore, for the survival of the tumor, it is enough to stop expressing these antigens. The new vaccine triggers an immune response against the HER2/neu protein, necessary for the survival of cells of early forms of breast cancer. Therefore, the destruction of this protein with the help of immune reactions should lead to the death of target cells.
HER2-new (human epidermal growth factor receptor 2) is a proto–oncogene encoding a type 2 human epidermal growth factor receptor. Overexpression of this gene in tumor tissue is found in about a third of breast cancer patients, which is associated with a poor prognosis. With overexpression of HER2 and locally advanced or metastatic breast cancer, therapy is prescribed using trastuzumab (herceptin), a drug based on monoclonal antibodies to this antigen, in the form of monotherapy or in combination with chemotherapy.
The study involved 27 women with HER2-positive ductal carcinomas in situ. Using standard apheresis technology, dendritic cells were isolated from their blood, which play an important regulatory role in the functioning of the immune system. These cells were activated and selectively stimulated using small fragments of the HER2/neu protein. Each patient received four injections of a personalized HER2 vaccine with a one-week interval between procedures. Two weeks after the last vaccination, the remaining tumor foci were surgically removed, which is the standard method of treating this disease.
Comparison of the biopsy samples isolated before vaccination with the material removed during the operation revealed striking changes. At the time of the operation, five patients had no visible signs of the disease, which indicated the complete destruction of the tumor by the immune system. In half (11) of the remaining 22 patients with signs of residual ductal carcinomas, HER2/neu expression was not recorded. According to Chernietski, comparable results have already been obtained in the course of the second clinical trial currently underway.
The study of the immune status of the patients showed that 85% of them contained CD4 and CD8 T-lymphocytes specific to HER2/neu, which indicates the stability and relative usefulness of post-vaccination immune reactions. It is also important to note that some women had antitumor immunity for 52 months, which indicates the presence of long-term protection against the appearance of aggressive relapses of the disease.
The results of the study indicate that the vaccine is safe and relatively easily tolerated by women. It causes only a number of mild side effects, the most common of which are a feeling of anxiety (72%), soreness at the injection site (59%), a feeling of cold or chills (38%), fever (28%) and headaches (24%).
The number of patients who took part in the study is relatively small, but Chernietski believes that over the next two years, the authors will already be able to assess the ability of the vaccine to prevent the recurrence of the disease. Currently, they are continuing to recruit patients for a larger clinical trial and are developing a strategy for testing the effectiveness of the vaccine against the early stages of invasive breast cancer. They also plan to create a vaccine with the addition of two additional antigens HER3 and HER1.
Chernietski also notes that the results obtained when working with ductal carcinoma in situ are applicable not only to the treatment of invasive breast cancer, but also to the treatment of other solid tumors whose cell functioning is impossible without signaling proteins of the HER family, including melanoma, lung cancer, brain and rectum.
Article by Sharma et al. HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ is published on-line in the journal Cancer, and an article by Koski et al. A Novel Dendritic Cell-based Immunization Approach for the Induction of Durable Th1-polarized Anti-HER-2/neu Responses in Women With Early Breast Cancer - in the January issue of the Journal of Immunotherapy.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Pennsylvania:
Four-Week Vaccination Regimen Knocks Out Early Breast Cancer Tumors, Penn Researchers Report.
01.02.2012